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Smooth muscle cell-specific knock out of Neuropilin-1 impairs postnatal lung development and pathological vascular smooth muscle cell accumulation

Zachary, IC; Mahmoud, M; Evans, I; Mehta, V; Pellet-Many, C; Paliashvili, K; (2019) Smooth muscle cell-specific knock out of Neuropilin-1 impairs postnatal lung development and pathological vascular smooth muscle cell accumulation. American Journal of Physiology - Cell Physiology , 316 (3) C424-C433. 10.1152/ajpcell.00405.2018. Green open access

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Abstract

Neuropilin 1 (NRP1) is important for neuronal and cardiovascular development due to its role in conveying class 3 semaphorin and vascular endothelial growth factor signalling, respectively. NRP1 is expressed in smooth muscle cells (SMCs) and mediates their migration and proliferation in cell culture, and is implicated in pathological SMC remodelling in vivo. To address the importance of Nrp1for SMC function during development, we generated conditional inducible Nrp1SMC-specific knockout mice. Induction of early postnatal SMC-specific Nrp1knockout led to pulmonary haemorrhage associated with defects in alveogenesis, and revealed a specific requirement for Nrp1in myofibroblast recruitment to the alveolar septae and PDGF-AA-induced migration in vitro. Furthermore, SMC-specific Nrp1knockout inhibited PDGF-BB-stimulated SMC outgrowth ex vivo in aortic ring assays, and reduced pathological arterial neointima formation in vivo. In contrast, we observed little significant effect of SMC-specific Nrp1knockout on neonatal retinal vascularisation. Our results point to a requirement of Nrp1in vascular smooth muscle and myofibroblast function in vivo, which may have relevance for post-natal lung development and for pathologies characterised by excessive SMC and/or myofibroblast proliferation.

Type: Article
Title: Smooth muscle cell-specific knock out of Neuropilin-1 impairs postnatal lung development and pathological vascular smooth muscle cell accumulation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1152/ajpcell.00405.2018
Publisher version: http://doi.org/10.1152/ajpcell.00405.2018
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Neuropilin-1, alveolar myofibroblast, SMC, neointima
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10066330
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